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Posted: November 5, 2009

CAREER award for contributions to stem cell analysis

(Nanowerk News) While a benefit of stem cells lies in their potential to develop into many cell types, that tendency to differentiate also frustrates researchers trying to study stem cells without disturbing them.

“Many stimuli — whether it be mechanical, electrical, chemical — can induce this differentiation,” says Biomedical Engineering Assistant Professor Brenda Ogle. “Often we don’t realize we’re inducing these changes, and so the cells have to be constantly monitored. The large numbers of cells to be analyzed, and the sensitivity of stem cells to external stimuli, makes this a difficult task.”

Recipient of a 2009 National Science Foundation CAREER award, Ogle is developing stem cell analysis tools that offer researchers the flexibility to study not only individual cells, but also multicellular entities and small tissue-engineered constructs.

One technology builds on a flow cytometer, an analysis tool in which large volumes of individual cells flow quickly through a chamber. There, a laser hits the cells and reflects light that provides researchers information about physical and chemical characteristics of a cell.

Called multi-photon flow cytometry, Ogle’s technology incorporates fluidics that can handle not only single cells, but also larger, multicellular aggregates or tissue-engineered constructs. In addition, it employs multiphoton optics that enable researchers to move beyond surface analysis and probe deep within the larger cellular structures. Only one company, Union Biometrica, currently manufactures a large-particle flow cytometry system that can accommodate multicellular structures, but the system’s optics limit researchers to studying just cell surfaces.

To develop their technology, Ogle and her students drew on UW-Madison experts in optics (Biomedical Engineering and Molecular Biology Assistant Scientist Kevin Eliceiri) and microfluidics (Biomedical Engineering Professor David Beebe and Assistant Professor Justin Williams).

The team has filed a patent application for the technology — an add-on to the current cytometer — through the Wisconsin Alumni Research Foundation. With the CAREER funding, Ogle and her students plan not only to improve their proof-of-concept prototype and share it with other stem cell researchers, but also use it to study stem cell fusion processes.

Ogle and others are exploring the therapeutic benefits of fusing stem cells with mature cells, such as cardiomyocytes, or heart muscle cells. While researchers have demonstrated cell fusion in vivo and in vitro, only recently have they begun to study how this fusion occurs. “We want to know what happens to cells that undergo fusion over time, and so a nice way to analyze them in a high-throughput way is with this multi-photon flow cytometer,” says Ogle.

She and her students also hope to develop sorting capabilities for the technology, so that if they or other researchers identify cells that exhibit certain properties, they can isolate, culture and study those cells separately.

Currently, the multi-photon flow cytometer resides in the campus Laboratory for Optical and Computational Instrumentation, and she aims to make it available to a broader range of researchers both on and off campus. Her efforts may lead to a consortium that enables member companies to collaboratively generate new technologies that advance stem cell biology and help translate stem cell research into commercial products.